CROI 2025 Abstract eBook

Abstract eBook

Poster Abstracts

986

Depression, Sleep, and Anxiety Among Pregnant and Postpartum Women Using Dolutegravir and Efavirenz Danni Wu 1 , Kristin Baltrusaitis 1 , Teacler Nematadzira 2 , Malinda Kaiyo-Utete 2 , Anne Coletti 5 , Katie McCarthy 6 , Chelsea Krotje 7 , Lameck Chinula 8 , Shahin Lockman 1 , Lynda Stranix-Chibanda 9 , for the IMPAACT 2010 (VESTED) Study Team 1 Harvard TH Chan School of Public Health, Boston, MA, USA, 2 University of Zimbabwe, Harare, Zimbabwe, 5 FHI 360, Lusaka, Zambia, 6 Family Health International 360, Durham, NC, USA, 7 Frontier Science & Technology Research Foundation, Inc, Amherst, NY, USA, 8 University of North Carolina Project–Malawi, Lilongwe, Malawi, 9 University of Zimbabwe Clinical Trials Research Centre, Harare, Zimbabwe Background: Dolutegravir (DTG) and Efavirenz (EFV) have been associated with neuropsychiatric symptoms, which may impact adherence to antiretroviral therapy (ART) in pregnant and postpartum people living with HIV. However, their impact on postpartum mental health remains insufficiently understood. We compared depression, sleep disturbances and anxiety between DTG and EFV treatment in pregnant and postpartum people living with HIV in nine countries. Methods: In IMPAACT 2010, pregnant people with HIV were randomized to DTG + emtricitabine (FTC)/tenofovir alafenamide (TAF), DTG+FTC/tenofovir disoproxil fumarate (TDF), or EFV/FTC/TDF arm at 14-28 weeks’ gestation and were followed through 50 weeks postpartum. Depression was assessed using the Edinburgh Postnatal Depression Scale (EPDS) at Postpartum (PP) Weeks 6 and 50. Sleep disturbances and anxiety were evaluated using the Pittsburgh Sleep Quality Index (PSQI) and Generalized Anxiety Disorder 7-item Scale (GAD-7) at Entry, Antepartum (AP) Week 8 and PP Week 38. Statistical modeling methods are detailed in Table 1. Results: 643 participants were randomized (432 to DTG and 211 to EFV), with a mean (standard deviation) age of 27.4 (6.0) years and 91.0% (585/643) as Black African. The depression proportion at PP Week 6 and/or 50 was 19.6% (82/419) in DTG and 17.6% (36/205) in EFV, with a difference (DTG - EFV) of 2.01% (95% confidence interval [CI]: -4.44%, 8.46%). The mean difference in EPDS scores was 0.33 (95% CI: -0.34, 1.01) at PP Week 6 (primary) and 0.06 (95% CI: -0.63, 0.74) at PP Week 50. The anxiety proportion at AP Week 8 and/or PP Week 38 was 4.7% (19/406) in DTG and 3.5% (7/198) in EFV among participants without anxiety at Entry. For GAD-7 scores, the mean difference was 0.18 (95% CI: -0.20, 0.57) at AP Week 8 and 0.41 (95% CI: -0.02, 0.85) at PP Week 38. The sleep disturbance proportion at AP Week 8 and/or PP Week 38 was 23.3% (62/266) in DTG and 24.8% (34/137) in EFV among participants without sleep disturbances at Entry. The mean difference in PSQI scores was 0.40 (95% CI: 0, 0.80) at AP Week 8 and 0.02 (95% CI: -0.41, 0.44) at PP Week 38. Conclusions: This study showed a similar proportion of depression, anxiety, and sleep disturbances between DTG and EFV, with roughly one in five women experiencing postpartum depression across all ART regimens. These findings highlight the importance of screening for mental distress in pregnant people living with HIV and considering postpartum well-being.

patterns and examined whether these patterns varied by HIV status or duration of DTG use. Finally, we used linear regression to examine whether GWG (change in weight between first and third trimester in kg/week) varied by HIV/DTG. Results: At enrolment, median age was 27y [Interquartile range (IQR), 24-32]; GA 10w [8-12]; BMI 30 kg/m 2 [25-35]; fat-mass index (FMI) 13kg/m 2 [9–17]; centripetal fat ratio (CPFR) 52 [47-56]. In WLH median duration of DTG use was 219 days [10-646] and 21% of women who initiated TLD were DTG naïve. LPA identified five distinct adiposity patterns: (i)normal weight/normal central fat, (ii)overweight/high central fat, (iii)obese/normal central fat, (iv)obese/low central fat, and (v)morbid obese/high central fat. While women in pattern (i) were significantly younger, neither HIV status nor DTG duration were different across adiposity patterns after adjusting for maternal age. Among 798 women (84%) with third trimester GWG assessment, GWG patterns varied by HIV and BMI (figure 1): WLH experienced 0.03 kg/week lower rate of GWG compared to HIV- women after adjustment for age, parity, education, GA and BMI at enrolment (95% CI: -0.06 to -0.01, p = 0.02). Restricted to WLH, GWG did not vary by TLD duration (not shown). Conclusions: These reassuring data suggest that DTG is not associated with GWG in this setting. While the patterns of adiposity identified are specific to this population, these are not associated with HIV/DTG. Genome-Wide Association With Postpartum Weight Change in Mothers on DTG or EFV in DolPHIN-2 Rebecca Jensen 1 , Ray Monk 1 , Thokozile R. Malaba 2 , Eunice Zhang 1 , Duolao Wang 3 , Sylvia Nassiwa 4 , Catriona Waitt 1 , Lucy Read 3 , Jim Read 3 , Helen E. Reynolds 1 , Catherine Orrell 2 , Landon Myer 2 , Daniel Carr 1 , Saye Khoo 1 , for the DolPHIN-2 Study Group 1 University of Liverpool, Liverpool, UK, 2 University of Cape Town, Cape Town, South Africa, 3 Liverpool School of Tropical Medicine, Liverpool, UK, 4 Makerere University, Kampala, Uganda Background: DolPHIN-2 (NCT 03249181) randomised mothers initiating ART in late pregnancy to efavirenz (EFV)- or dolutegravir (DTG) based regimens. We previously reported no significant differences between arms in weight change post-delivery to 48w postpartum (PP), but observed heterogeneity with numerically greater weight gain in women from South Africa. Here, we undertook a genome-wide association study (GWAS) to identify genetic variants associated with weight change from delivery to 48w PP. Methods: 159 participants were genotyped using the Illumina Infinium™ H3Africa Consortium Array v2 (2.27million variants) and after quality control of the genotyped data, 129 mothers (62 EFV, 67 DTG) were included with 1.8 million variants analysed to identify genes related to weight change, with adjustments for age and the first four principal components. Weights were recorded using standardised procedures at enrolment, <14 days of delivery and at 6, 12, 24 and 48 weeks PP. Weight change was calculated as a percentage from delivery to 48w PP. Results: Analysis identified 21 loci which reached the suggestive genome-wide threshold ( p < 1 x 10 −5 ). The top three associated loci were EMB ( p , 2.4 x10 -7 ), LINC02710 ( p , 4.0 x10 -7 ), and AL365440 .2 (p, 6.3 x10 -7 ). One of the statistically significant loci associated with weight gain was related to the HK1 gene ( p , 9.7 x10 -6 ; 95% CI 0.24-0.60; β 0.42) which encodes hexokinases that are involved in the first step of glucose metabolism pathways and could offer a possible explanation for weight changes. Conclusions: These findings suggest that there are genetic variants which may be associated with changes in postpartum weight in women receiving DTG- or EFZ-based treatments. Further work is underway to undertake genotype imputation across the whole human genome which will allow us to identify potential causal variants associated with DTG- or EFZ-induced postpartum weight change. Data stratification by treatment group will also be carried out to see if any genes are specifically related to DTG- or EFZ-based treatment. The figure, table, or graphic for this abstract has been removed.

985

Poster Abstracts

CROI 2025 312